IONIS PHARMACEUTICALS INC Q2 FY2025 earnings call

• Brett Monia highlighted strong momentum across the business, including excellent early commercial performance of Tryngolza, increase in financial guidance for 2025, and progress with Donidalorsen and Phase III pipeline. - Kyle Jenne discussed Tryngolza's launch performance, patient identification efforts, commercial strategy, and progress on Olezarsen and Donidalorsen. - Richard Geary provided pipeline updates, including ESSENCE study results, Zilganersen progress, and addition of ION582. - Beth Hougen discussed financial results, revenue guidance increase, operating expenses, and cash flow management.

Tryngolza generated $19 million in net product sales in the second quarter, a threefold increase quarter-over-quarter. Royalty revenues increased by approximately 10% to $70 million in the second quarter, anchored by contributions from SPINRAZA and Wainua. Revenue from R&D collaborations, including a $280 million upfront payment for the sapablursen license, also contributed. Tryngolza's revenue contribution is significant, with its strong commercial performance supporting the increased financial guidance for 2025.

• Increased revenue guidance for 2025 to $850 million, an increase of $100 million from prior guidance. - Expect Tryngolza product sales to be between $75 million and $80 million in 2025. - Donidalorsen is expected to modestly contribute to revenues in 2025 with greater contribution in 2026 due to FDA action date of August 21. - Project operating loss between $300 million and $325 million and year-end cash balance of approximately $2 billion for 2025.

• Regulatory uncertainties related to approval timelines and label contents. - Uncertainty around AP event data and its impact on market reception. - Payer dynamics and competition affecting pricing and market penetration. - Operational risks associated with clinical trial timelines and data readouts.

Q: Talk about how the Tryngolza FCS launch is going in terms of finding new patients and reimbursement.

A: Kyle Jenne mentioned strong early momentum, over 3,000 physicians interacted with, patient out-of-pocket expenses low, and continued patient identification efforts.

Q: On sHTG readout in September, what trig lowering expected?

A: Brett Monia said expected 58%-62% reduction, with anything north of 50% a big win.

Q: On Donidalorsen PDUFA on August 21, labeling discussions?

A: Richard Geary said on track for PDUFA date, labeling a matter of negotiation but launch preparations in place.

Q: On CORE and CORE2 AP events?

A: Brett Monia said accumulated AP events in CORE and CORE2 combined will be more than in FCS BALANCE study, but exact details pending data readout.

Q: On Tryngolza guidance $75M-$80M, color on new patient add-on?

A: Kyle Jenne said it takes time to identify newly diagnosed patients in the FCS population, focusing on penetration into the potential 3,000-patient population.

Q: On uptake of drug outside US?

A: Kyle Jenne discussed regulatory and payer dynamics outside US, noting positive CHMP opinion for EU and partnership with Sobi for FCS in Europe.

Q: On early stage pipeline vs out-licensing?

A: Brett Monia said priority is wholly owned pipeline, but will partner on assets outside focus areas.

Q: On ex US infrastructure for global launches?

A: Brett Monia said focus is on US launches first, will consider ex US infrastructure later as needed.